Serotherapy with thymoglobulin and alemtuzumab differentially influences frequency and function of natural killer cells after allogeneic stem cell transplantation Journal Article

  

Authors:	Penack, O.; Fischer, L.; Stroux, A.; Gentilini, C.; Nogai, A.; Muessig, A.; Rieger, K.; Ganepola, S.; Herr, W.; Meyer, R. G.; Thiel, E.; Uharek, L.
Article Title:	Serotherapy with thymoglobulin and alemtuzumab differentially influences frequency and function of natural killer cells after allogeneic stem cell transplantation
Abstract:	Although thymoglobulin and alemtuzumab are frequently used in hematopoietic stem cell transplantation ( HSCT), little is known of their effects on NK cells, which mediate important functions in post-transplantation immunology. In the present study, we determined NK cell death in vitro using propidium iodide and Annexin V. The NK cell activity in 34 patients at day +30 after allogeneic HSCT was assessed using the CD107a assay. Alemtuzumab and thymoglobulin were similarly very potent in inducing NK cell death in vitro. Even in low concentrations (<1 mu g/ml) the antibodies induced apoptosis and necrosis in a relevant percentage of NK cells ( >30%). However, the number of tumor reactive ( CD107a+) NK cells was 13.16 per mu l and 1.15 per mu l ( mean) in patients receiving T-cell depletion with 6 mg/ kg thymoglobulin and in patients receiving 100 mg alemtuzumab, respectively ( P=0.02). Although thymoglobulin and alemtuzumab are equally NK cell toxic in vitro, the recovery of NK cell frequency and anti-tumor reactivity is reduced in recipients of alemtuzumab. Our findings can be explained by a longer half-life of alemtuzumab as compared to active thymoglobulin under therapeutic conditions. Prolonged immunosuppression with increased risk of infections and tumor relapse are a potential threat to patients undergoing HCST and receiving alemtuzumab as T-cell depletion.
Keywords:	leukemia; alemtuzumab; pharmacokinetics; versus-host-disease; immune reconstitution; bone-marrow; hsct; recipients; annexin-v; anti-thymocyte globulin; natural killer cells; phosphatidylserine expression; thymoglobulin; flow-cytometric detection
Journal Title:	Bone Marrow Transplantation
Volume:	41
Issue:	4
ISSN:	0268-3369
Publisher:	Nature Publishing Group
Date Published:	2008-02-01
Start Page:	377
End Page:	383
Language:	English
ACCESSION:	WOS:000253548500008
DOI:	10.1038/sj.bmt.1705911
PROVIDER:	wos
PUBMED:	17982494
Notes:	--- - Article - "Source: Wos"

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